Adding calorimetric data to decision making in lead discovery: a hot tip

Abstract

Recognition of the limitations of high-throughput screening approaches in the discovery of candidate drugs has reawakened interest in structure-based and other rational design methods. Here, we describe how isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. We propose that these data--particularly the change in enthalpy--could provide a valuable, complementary addition to established tools for selecting compounds in lead discovery and for aiding lead optimization.